Methotrexate treatment hampers induction of vaccine-specific CD4 T cell responses in patients with IMID.

IF 5.1 2区 医学 Q1 RHEUMATOLOGY RMD Open Pub Date : 2024-10-07 DOI:10.1136/rmdopen-2024-004664
Laura Y L Kummer, Laura Fernández Blanco, Christine Kreher, Amélie Bos, Lisan H Kuijper, Niels J M Verstegen, Carolien E van de Sandt, Veronique A L Konijn, Mariël C Duurland, Charlotte Menage, Tineke Jorritsma, Maurice Steenhuis, Ruth R Hagen, Jet van den Dijssel, Rivka de Jongh, Tom Ashhurst, Marit J van Gils, Juan J Garcia-Vallejo, Mathieu Claireaux, Eileen W Stalman, Koos P J van Dam, Luuk Wieske, Laura Boekel, Gertjan Wolbink, Sander W Tas, Theo Rispens, Taco W Kuijpers, Filip Eftimov, Sija Marieke van Ham, Anja Ten Brinke
{"title":"Methotrexate treatment hampers induction of vaccine-specific CD4 T cell responses in patients with IMID.","authors":"Laura Y L Kummer, Laura Fernández Blanco, Christine Kreher, Amélie Bos, Lisan H Kuijper, Niels J M Verstegen, Carolien E van de Sandt, Veronique A L Konijn, Mariël C Duurland, Charlotte Menage, Tineke Jorritsma, Maurice Steenhuis, Ruth R Hagen, Jet van den Dijssel, Rivka de Jongh, Tom Ashhurst, Marit J van Gils, Juan J Garcia-Vallejo, Mathieu Claireaux, Eileen W Stalman, Koos P J van Dam, Luuk Wieske, Laura Boekel, Gertjan Wolbink, Sander W Tas, Theo Rispens, Taco W Kuijpers, Filip Eftimov, Sija Marieke van Ham, Anja Ten Brinke","doi":"10.1136/rmdopen-2024-004664","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.</p><p><strong>Methods: </strong>In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3-6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.</p><p><strong>Results: </strong>Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.</p><p><strong>Conclusion: </strong>Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.</p><p><strong>Trial registration number: </strong>NL8900.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459311/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"RMD Open","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/rmdopen-2024-004664","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objectives: Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.

Methods: In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3-6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.

Results: Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.

Conclusion: Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.

Trial registration number: NL8900.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
甲氨蝶呤治疗阻碍了 IMID 患者对疫苗特异性 CD4 T 细胞反应的诱导。
目的:甲氨蝶呤(MTX)是治疗类风湿性关节炎(RA)最常用的药物之一。然而,人们对 MTX 治疗对细胞免疫反应的影响仍不甚了解。这引发了人们对这些患者易受新发感染和接种疫苗后的脆弱性的担忧:在本研究中,我们调查了MTX治疗对免疫介导的炎症性疾病患者B细胞和CD4 T细胞SARS-CoV-2疫苗接种反应的影响。研究对象包括 18 名接受 MTX 单药治疗的 RA 患者和两名银屑病关节炎患者,以及 10 名未接受免疫抑制治疗的 RA 患者和 29 名健康对照者。在两次接种 SARS-CoV-2 信使 RNA 疫苗 7 天和 3-6 个月后,对 CD4 T 细胞和 B 细胞反应进行了分析。使用高维流式细胞仪分析新鲜全血,使用活化诱导标记测定法测量抗原特异性 CD4 T 细胞,使用尖峰探针研究抗原特异性 B 细胞:结果:接种两次 SARS-CoV-2 疫苗七天后,MTX 治疗患者和对照组的 B 细胞和 T 细胞总数相似。此外,尖峰特异性 B 细胞频率未受影响。值得注意的是,在使用 MTX 的患者中,抗原特异性 CD4 T 细胞的频率降低,并且与抗 RBD IgG 抗体密切相关。这些结果表明,CD4 T细胞活性的降低可能会导致MTX治疗患者的疫苗抗体反应变慢:综上所述,MTX 治疗可降低疫苗诱导的 CD4 T 细胞活化,这与抗体反应较低有关:NL8900.
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
RMD Open
RMD Open RHEUMATOLOGY-
CiteScore
7.30
自引率
6.50%
发文量
205
审稿时长
14 weeks
期刊介绍: RMD Open publishes high quality peer-reviewed original research covering the full spectrum of musculoskeletal disorders, rheumatism and connective tissue diseases, including osteoporosis, spine and rehabilitation. Clinical and epidemiological research, basic and translational medicine, interesting clinical cases, and smaller studies that add to the literature are all considered.
期刊最新文献
Arthritis progressors have a decreased frequency of circulating autoreactive T cells during the at-risk phase of rheumatoid arthritis. Gut microbiota in very early systemic sclerosis: the first case-control taxonomic and functional characterisation highlighting an altered butyric acid profile. Fibroblast-like synoviocyte targeting antibodies are associated with failure to reach early and sustained remission or low disease activity after first-line therapy in rheumatoid arthritis. Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial. Immune checkpoint molecules performance in ANCA vasculitis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1